Carboplatin (hereinafter also referred to as "CBDCA" or CBP") is a widely used anticancer drug which is normally used in combination with other anticancer drugs in the treatment of cancers of the lung, head and neck, ovary, esophagus, bladder, testis, and others. One of the most important and common dose limiting toxicities of carboplatin is hematological toxicity. In particular, myelosuppression (depression of blood elements formed within bone marrow) is often manifested in the form of thrombocytopenia, neutropenia, leukopenia, and various forms of anemia. The other major carboplatin-induced toxicity is gastro-intestinal (causing nausea and vomiting).
In order for carboplatin to react with certain nucleic acid sequences in cellular DNA, it must first undergo chemical conversion to an active species by the partial or complete displacement of the cyclobutanedicarboxylato (CBDC) ligands, respectively, by chloride. The chloro and dichloro species are believed to act against cancer cells by reacting with the imidazole nitrogens on DNA. These chloro species are believed to be metabolised in vivo to active hydroxy species.
Carboplatin, unlike cisplatin, is relatively stable in the body. Its cyclobutanedicarboxylato (CBDC) group makes it much less susceptible to displacement by incoming nucleophiles. It is less active than cisplatin towards DNA. Indeed, it is generally given in combination with other anti-cancer drugs. Although less prone to cause the nephrotoxicity associated with cisplatin, it is highly myelotoxic and has gastrointestinal toxicity. It might at first be thought that carboplatin, with its active chloro species, should behave similarly to cisplatin and therefore be further metabolised in the same way. However, this is not so: the body cells most adversely affected by carboplatin-induced toxicity (bone marrow and GI tract cells) are different from those most adversely affected by cisplatin (kidney cells). Thus, the metabolic species responsible for the toxicity cannot be the same. Finding a protective agent for carboplatin therefore represents a new and separate problem from that presented by cisplatin.